The long-term goal of the Breast Cancer (BC) Program is to apply this knowledge of biology, genetics and biochemistry of breast cancer towards diagnostic, therapeutic and preventive strategies. To achieve this end, the following Specific Goals will be pursued: 1) To identify aberrant regulatory pathways in breast cancer pathogenesis. Specifically, by analyzing tumor biopsies and model systems, we will dissect the pathways responsible for distinct subtypes of breast cancer and elucidate their mechanistic role in tumor development. 2) To optimize the treatment and prevention of breast cancer. By using tissue, serum and imaging-based biomarkers, we will identify suitable patients for targeted therapy and then measure its efficacy. 3) To improve the quality of breast cancer care. By using novel methodologies to characterize the short and long term risks associated with standard breast cancer treatment, we will conduct clinical trials to evaluate novel interventions to diminish these effects. Since the prior grant period, the number of institution-based clinical trials in breast cancer and the number of patients accrued to therapeutic and supportive care trials has increased, with 5 investigators leading a total of 8 NCI Cooperative Group Trials. The number of new breast cancer cases averaged 437/year; of these, 66 patients/year (peak 76) enrolled on therapeutic clinical trials (15%) and 135 patients/year patients accrued to non-therapeutic interventional trials per year (31%). The majority of these clinical trials were investigator initiated and 48% of patients accrued were minorities. The BC program consists of 28 members (19 full) from eleven departments within the College of Physicians & Surgeons, the Mailman School of Public Health and Biomedical Engineering at Columbia University. The Program is enhanced by large program project grants, including a breast cancer NCI POI focused on signaling pathways in triple negative breast cancer and a DOD Center of Excellence focused on disparities in breast cancer treatment. For the last budget period of the grant (July 1, 2012 - June 30, 2013), the BC Program received a total of $6.48M (direct costs) in cancer-relevant grant support, including $2.48M (direct costs) in NCI funding, $2.84M (direct costs) in other cancer-related peer-reviewed funding, and $1.21M (direct costs) in cancer-related non-peer-reviewed funding. The total number of publications since the previous submission (i.e., 2008-present) was 366, of which 13% were intra-programmatic, 39% inter-programmatic and 21% were in high impact journals (Impact Factor >10).